Syphilis

Venereal syphilis is a contagious, systemic disease caused by Treponema pallidum. T. pallidum enters via abraded skin or intact mucous membrane and distributes via the blood stream and lymphatics after an incubation period of around 3 weeks (range 2-6 weeks).

• Early syphilis causes significant morbidity and is an important facilitator of HIV transmission.
• All patients diagnosed with syphilis must be tested for HIV, and those having follow-up for HIV must have regular screening for syphilis.
• Congenital syphilis is a major cause of stillbirth, childhood morbidity, and mortality worldwide.¹
• Syphilis is classified as acquired or congenital.

• Primary syphilis: incubation period 2-3 weeks (range 9-90 days): local infection
• Secondary syphilis: incubation period 6-12 weeks (range 1-6 months): generalised infection
• Early latent syphilis: asymptomatic syphilis of less than 2 years duration
• Late latent syphilis: asymptomatic syphilis of 2 years or longer duration
• Late symptomatic syphilis (tertiary syphilis): cardiovascular syphilis, neurosyphilis, gummatous syphilis

• Early congenital syphilis occurs within the first 2 years of life.
• Late congenital syphilis emerges in children older than 2 years.

• In 2003, there were 1,580 cases diagnosed in STD clinics in England, Wales and Northern Ireland. The highest rates of syphilis are seen in women aged 20-24 and men aged 25-34 years.²
• The tertiary stage is now rarely seen in the UK, possibly because those affected many years ago have received antibiotics for other infections in the intervening time.³

Primary syphilis

• Primary lesion develops at the site of infection, which heals in 2-6 weeks.
• Small, painless papule that rapidly forms an ulcer (the chancre). The chancre is usually single, round or oval, painless, surrounded by a bright red margin and indurated with a clean base, and discharging clear serum.
• Chancres may be atypical, e.g. multiple, painful, purulent, destructive and may be extra-genital.
• Usually found in heterosexual men on the coronary sulcus, the glans and inner surface of the prepuce but may appear on the shaft and beyond. In homosexual men, usually found in the anal canal and less frequently in the mouth and genitalia. In women, found on the vulva, labia and much less frequently on the cervix.
• Extra-genital sites are the lips, mouth, buttocks and fingers.
• Enlarged regional lymph nodes that are painless, discrete, firm and not fixed to surrounding tissues.

Secondary syphilis

• Secondary syphilis often appears 6 weeks after the beginning of the primary lesion but may overlap or not appear for several months.
• Multisystem involvement occurs within the first two years of infection.
• Systemic symptoms are mild or absent, but include night time headaches, malaise, slight fever and aches.
• A generalised polymorphic rash often affects the palms, soles and face. The rash is classically non-itchy but may be itchy, especially in dark-skinned patients. It is associated with generalised painless lymphadenopathy.
• Papules enlarge into condylomata lata (pink or grey discs) in moist warm areas. Papule lesions disappear spontaneously.
• There may also be mucocutaneous lesions.
• Less common presentations include patchy alopecia, anterior uveitis, meningitis, cranial nerve palsies, hepatitis, splenomegaly, periosteitis and glomerulonephritis.
• In 80% of cases, patients enter the latent asymptomatic stage which for over half of them persists for life. In about 20% of patients, an infectious relapse occurs during the next year.

Early latent syphilis

• Characterised by positive serological tests for syphilis with no clinical evidence of treponemal infection within the first two years of infection.

Late latent syphilis

• Infection of more than two years duration diagnosed on serological testing with no symptoms or signs of late manifestations of syphilis.
• Studies of cohorts of untreated patients suggest that symptomatic late syphilis is found in up to 40% of individuals with late T.pallidum infection.

Tertiary syphilis

This consists of three major clinical manifestations, which may co-exist:

• Neurological syphilis:
  • Asymptomatic neurosyphilis: late syphilis with abnormal CSF examination but with no associated neurological symptoms or signs.
  • Symptomatic neurosyphilis: the most common presentations are dorsal column loss (tabes dorsalis), dementia (general paralysis of the insane) and meningovascular involvement.
• Cardiovascular syphilis:
  • Characterised by an aortitis, which usually involves the aortic root but may affect other parts of the aorta usually spreading distally from the aortic root.
  • The most frequent clinical manifestations are aortic regurgitation, aortic aneurysm and angina.
• Gummata:
  • Inflammatory fibrous nodules or plaques, which may be locally destructive.
  • Can occur in any organ but most commonly affect bone and skin.

• Herpetic ulcers (especially chronic mucocutaneous anogenital herpes occurring with HIV infection)
• Chancroid
• Lymphogranuloma venereum
• Donovanosis

Investigations must include a screen for all sexually transmitted infections as well as investigation for other possible diagnoses.

• Treponemal tests (the TPHA test and the TPPA test are generally used for screening):⁴
  • T. pallidum particle agglutination assay (TPPA): incubation period 4-6 weeks (incubation period is the usual time after infection that the test becomes positive).
  • T. pallidum haemagglutination assay (TPHA): incubation period is 4-6 weeks.
  • Enzyme immunosorbant assay (EIA) IgG/IgM: incubation period is 3 weeks.
  • Fluorescent treponemal antibody absorption (FTA-ABS) test; is reactive in 85% of primary cases, in 99-100% of secondary cases, and in 95% of latent or late cases. It should be used as a confirmatory test for positive VDRL or RPR test findings.⁴
• Non-treponemal tests; give a titre that acts as measure of disease activity, i.e. the titre is reduced with treatment and raised with reinfection. False positives occur with other acute and chronic infections and autoimmune diseases.
  • Rapid plasma reagin (RPR): incubation period is 4 weeks.
  • Venereal Disease Reference Laboratory (VDRL): incubation period is 4 weeks.
  • Serological tests cannot differentiate from other treponemal infections, e.g. yaws (caused by the non-sexually transmitted organism T. pertenue).
• Demonstration of T. pallidum:
  • From lesions or infected lymph nodes in early syphilis
  • Dark field microscopy
  • Direct fluorescent antibody (DFA) test
  • Polymerase chain reaction (PCR)

• Treatment should be within an STD clinic with enquiries about sexual contacts.
• Patients who acquire syphilis are at significant risk of reinfection, and should therefore be regularly screened for syphilis and given sexual health promotion. All patients should be offered screening for other sexually transmitted infections, including HIV.

Drugs

Recommended regimes for adults:¹

• Primary, secondary, early latent syphilis: benzathine penicillin 2.4 megaunits (intramuscular, single dose), or procaine penicillin 600 000 units (intramuscular, once daily for 10 days). Alternatively doxycycline 100 mg twice daily for 14 days. 2 g oral azithromycin has been shown to be as effective in treating early syphilis as benzathine penicillin.
• Late latent syphilis: benzathine penicillin 2.4 megaunits (intramuscular, three injections spaced weekly over 2 weeks), or procaine penicillin 900 000 units (intramuscular, daily for 17 days). Alternatively doxycycline 200 mg twice daily for 28 days.
• Neurosyphilis: procaine penicillin 2.4 units once daily (intramuscular, for 17 days) with oral probenecid 500 mg four times a day. Alternatively doxycycline 200 mg twice daily for 28 days.
• Pregnancy:
  • First line: IM Procaine penicillin G.
  • Penicillin allergy: erythromycin or azithromycin. Consider those treated with erythromycin or azithromycin for retreatment with doxycycline after delivery and when breast-feeding is stopped.

Jarisch-Herxheimer reaction

• Is a reaction to treatment.⁵
• An acute febrile illness with headache, myalgia, chills and rigors and resolving within 24 hours.
• Common in early syphilis but is usually not important unless there is neurological or ophthalmic involvement or in pregnancy when it may cause fetal distress and premature labour.
• It is uncommon in late syphilis but may be life threatening.
• Treatment is with prednisolone and antipyretics.

• Treatment of asymptomatic contacts
• Use of condoms

• In pregnant women with untreated early syphilis, 70-100% of infants will be infected with stillbirths in up to one-third of cases.⁵
• Diagnosis:
  • Early (first two years): rash including condylomata lata, vesiculobullous lesions, snuffles, haemorrhagic rhinitis, osteochondritis, periostitis, pseudoparalysis, mucous patches, perioral fissures, hepatosplenomegaly, generalised lymphadenopathy, glomerulonephritis, neurological or ocular involvement, haemolysis, thrombocytopenia.
  • Late including stigmata: interstitial keratitis, Clutton's joints (arthritis of knees), Hutchinson's incisors, mulberry molars, high palatal arch, rhagades, deafness, frontal bossing, short maxilla, protuberance of mandible, saddle nose deformity, sterno-clavicular thickening, paroxysmal cold haemoglobinuria, neurological or gummatous involvement.
• Investigations:
  • Serological tests that detect IgG may be positive due to passive transfer of maternal antibodies.⁶
  • A positive anti-treponemal EIA IgM is indicative of congenital infection.
  • Serological tests may be negative in infants infected in late pregnancy and should be repeated.
• Treatment:
  • Intravenous benzyl penicillin for the first ten days of life.
  • Older siblings should be screened for congenital syphilis.
  • Congenital syphilis diagnosed in an older child or in adulthood should be managed as for late syphilis.
  • Parents, all siblings and any sexual partner should be screened for syphilis.